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Nead, K.T.* ; Li, A.* ; Wehner, M.R.* ; Neupane, B.* ; Gustafsson, S.* ; Butterworth, A.S.* ; Engert, J.C.* ; Davis, A.D.* ; Hegele, R.A.* ; Miller, R.* ; den Hoed, M.* ; Khaw, K.T.* ; Kilpeläinen, T.O.* ; Wareham, N.J.* ; Edwards, T.L.* ; Hallmans, G.* ; Varga, T.V.* ; Kardia, S.L.* ; Smith, J.A.* ; Zhao, W.* ; Faul, J.D.* ; Weir, D.R.* ; Mi, J.* ; Xi, B.* ; Quinteros, S.C.* ; Cooper, C.* ; Sayer, A.A.* ; Jameson, K.* ; Grøntved, A.* ; Fornage, M.* ; Sidney, S.* ; Hanis, C.L.* ; Highland, H.M.* ; Häring, H.-U. ; Heni, M.* ; Lasky-Su, J.* ; Weiss, S.T.* ; Gerhard, G.S.* ; Still, C.* ; Melka, M.M.* ; Pausova, Z.* ; Paus, T.* ; Grant, S.F.A.* ; Hakonarson, H.* ; Price, R.A.* ; Wang, K.* ; Scherag, A.* ; Hebebrand, J.* ; Hinney, A.* ; BIoBank Japan (Meyre, D.*) ; GIANT Consortium (Albrecht, E. ; Gieger, C. ; Grallert, H. ; Heid, I.M. ; Illig, T. ; Müller-Nurasyid, M. ; Peters, A. ; Thorand, B. ; Wichmann, H.-E.) ; Franks, P.W.* ; Frayling, T.M.* ; McCarthy, M.I.* ; Hirschhorn, J.N.* ; Loos, R.J.* ; Ingelsson, E.* ; Gerstein, H.C.* ; Yusuf, S.* ; Beyene, J.* ; Anand, S.S.*

Contribution of common non-synonymous variants in PCSK1 to body mass index variation and risk of obesity: A systematic review and meta-analysis with evidence from up to 331 175 individuals.

Hum. Mol. Genet. 24, 3582-3594 (2015)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Polymorphisms rs6232 and rs6234/rs6235 in PCSK1 have been associated with extreme obesity [e.g. body mass index (BMI) ≥ 40 kg/m(2)], but their contribution to common obesity (BMI ≥ 30 kg/m(2)) and BMI variation in a multi-ethnic context is unclear. To fill this gap, we collected phenotypic and genetic data in up to 331 175 individuals from diverse ethnic groups. This process involved a systematic review of the literature in PubMed, Web of Science, Embase and the NIH GWAS catalog complemented by data extraction from pre-existing GWAS or custom-arrays in consortia and single studies. We employed recently developed global meta-analytic random-effects methods to calculate summary odds ratios (OR) and 95% confidence intervals (CIs) or beta estimates and standard errors (SE) for the obesity status and BMI analyses, respectively. Significant associations were found with binary obesity status for rs6232 (OR = 1.15, 95% CI 1.06-1.24, P = 6.08 × 10(-6)) and rs6234/rs6235 (OR = 1.07, 95% CI 1.04-1.10, P = 3.00 × 10(-7)). Similarly, significant associations were found with continuous BMI for rs6232 (β = 0.03, 95% CI 0.00-0.07; P = 0.047) and rs6234/rs6235 (β = 0.02, 95% CI 0.00-0.03; P = 5.57 × 10(-4)). Ethnicity, age and study ascertainment significantly modulated the association of PCSK1 polymorphisms with obesity. In summary, we demonstrate evidence that common gene variation in PCSK1 contributes to BMI variation and susceptibility to common obesity in the largest known meta-analysis published to date in genetic epidemiology.
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Publication type Article: Journal article
Document type Review
Corresponding Author
Keywords Genome-wide Association; Early-onset Obesity; Cardiovascular-disease; Genetic Association; Chinese Population; Identifies Common; Health-assessment; Extreme Obesity; Adult Obesity; Confer Risk
ISSN (print) / ISBN 0964-6906
e-ISSN 1460-2083
Journal Human Molecular Genetics
Quellenangaben Volume: 24, Issue: 12, Pages: 3582-3594 Article Number: , Supplement: ,
Publisher Oxford University Press
Publishing Place Oxford
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology II (EPI2)
Institute of Genetic Epidemiology (IGE)
Institute of Diabetes Research and Metabolic Diseases (IDM)